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Research Targets

Early Diagnosis | Surgical Management | New Therapies
Endoscopic Therapies | Quality of Life | Proteomics | Gene Identification

Our researchers are keeping pace with and, in fact, advancing the frontiers of clinical care. The genes that can cause pancreatic cancer are being sought. This will help further define which family members are affected. When a genetic test to diagnose hereditary pancreatic cancer is discovered, it may also prove useful in the more common non-hereditary types of pancreatic cancer. Epidemiologic studies at the University of Washington and the Fred Hutchinson Cancer Research Center have uncovered risk factors, such as smoking and exposure to dry cleaning fluids, which can dramatically influence the cancer risk of patients who have a positive family history. Similar environmental factors may be found in the more common non-familial pancreatic cancers. Exciting basic research and clinical trials are ongoing to develop even better methods of early diagnosis, prevention and treatment.

Early Diagnosis in High-Risk Patients

A number of different cancers may involve the pancreas. These include pancreatic adenocarcinoma (the most common cancer involving the pancreas), islet tumors of the pancreas, and cancers of the bile duct and duodenum. Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States. It appears to be increasing in frequency and in many cases has a genetic predisposition. It is clearly hereditary in 5-10% of cases; the risk of pancreatic cancer is increased 3-fold if one first-degree relative is affected. Having multiple affected members increases the risk even more, so that some family members have a 50-50 chance of inheriting pancreatic cancer. How will we provide cancer surveillance for these people who have family members who developed the disease?

Surgical Management

Currently, the only chance of a cure for pancreatic cancer is with surgery, though other treatments may have additional (adjuvant) benefit. The role of the surgeon is to educate and guide patients and their families through surgical treatment of pancreatic cancer, and to evaluate combined treatments and techniques for improving the safety and effectiveness of surgical therapy. Examples of such treatment include innovative pre-surgical treatment with chemotherapy and/or radiation, intraoperative radiation in selected circumstances, new surgical diagnostic techniques for evaluating the true extent of the cancer, and defining the appropriate role of radical surgical therapy.

Removal of the Pancreas:

For patients who have been found through surveillance studies to have a high risk of pancreatic cancer, the only effective current treatment is removal of the pancreas, usually completely. When performed before the development or spread of invasive adenocarcinoma, this treatment is curative. Unfortunately, most patients are found to have pancreatic adenocarcinoma when the cancer is quite advanced and causing symptoms. Even in this group of patients, if the cancer is confined to the pancreas and not involving regional vital structures such as major blood vessels, some patients can be cured by removal of the cancer, the surrounding region of normal pancreas, and regional lymph nodes. Since these lymph nodes run with the regional blood supply, surgery of this nature often requires removal of adjacent structures that share blood supply with the tumor.

The Whipple Procedure:

Most cancers of the pancreas develop in the head of the pancreas where 55% of the pancreatic mass is found. Regional resection of a pancreatic cancer developing in the head of the pancreas requires removal of the duodenum, part of the bile duct, and often part of the stomach. This is termed a Whipple procedure. The Whipple procedure has over a hundred steps and often takes 6 to 9 hours to complete since the gastrointestinal tract must be reconstructed after the removal of the tumor. Tumors involving the body or tail of the pancreas are often harder to diagnose, more advanced when detected, and more difficult to cure. Again, when confined to the pancreas and regional tissues, surgical removal (usually including the spleen which shares blood supply and lymph node drainage) is termed a distal pancreatectomy and offers a chance of cure.

For both the Whipple and distal pancreatectomy, surgery is clearly only part of the answer since cure rates are at best 1 in 3 to 1 in 4 of all patients surgically treated and only a minority of patients are even candidates for surgery. Because of this overall poor cure rate with surgery, our oncologic surgeons work in close partnership with cancer biologists, medical and radiation oncologists, and our colleagues in radiology and pathology to use surgical techniques and biopsies to study the cancer, to deliver innovative therapies to the cancer directly, and to understand and improve the effectiveness of our cancer treatment. Most of the same issues apply to other cancers of the pancreas such as islet tumors, though adenocarcinoma remains the focus of study.

New Therapies

In patients who are operable, clinical investigation has focused on novel combination of chemotherapeutic agents and radiation therapy with new potent radio-sensitizers (drugs that predispose the cancer to radiation) either pre-operatively or post-operatively. For patients who are not candidates for resection but do not have spread of their cancer (metastatic disease), a combination of chemotherapy/radiation regimens can be used. Clinical trials in these settings are a high priority. It is our goal to incorporate other strategies such as inhibition of tumor blood supply (anti-angiogenic therapy), immunotherapy or molecular targeted approaches in both early and late staged disease.

Endoscopic Therapies

Gastrointestinal endoscopy plays an integral role in the management of patients with pancreatic cancer. Endoscopic ultrasound is a noninvasive test that is more accurate than CT and MRI scanning for staging the local extent of disease and resectability. A tissue diagnosis can also usually be confirmed using endoscopic ultrasound guided biopsy of the pancreas. Endoscopic ultrasound can also allow placement of a needle into the celiac plexus for injection of alcohol to relieve pain caused by pancreatic cancer.

Patients with pancreatic cancer often present with jaundice. This can cause itching and discomfort which is relieved by placing a stent or tube in the bile duct using endoscopy. If the cancer blocks the intestine, a tube can also be placed using endoscopy to relieve the obstruction and allow the patient to eat. Both of these treatments are done through an instrument placed through the patient's mouth on an outpatient basis. Recovery time is much faster using these endoscopic methods when compared to surgery.

We have expert endoscopists who routinely perform all of these endoscopic procedures. They are also developing new endoscopic devices and conducting research studies to improve the diagnostic and treatment capabilities of endoscopy for patients with pancreatic cancer.

Quality of Life

Pancreatic cancer has a profound effect on individual and family quality of life. We have specialists who can address ‘the whole person’ with cancer and their family, including pain management, supporting individual and family coping, nutrition, spiritual concerns, and mental health concerns. Our researcherse are developing ways to help patients and families cope better, communicate better with their physicians, and improve quality of life for pancreatic cancer patients and their families. New studies will examine the impact of genetic findings on family member quality of life.

Proteomics

Pancreatic cancer is difficult to detect and difficult to treat. The problem of early diagnosis is complex and complicated by the obscure location of the pancreas, the absence of reliable symptoms and the insensitivity and expense of current tests. What is needed are better methods of determining who is at risk, and more accurate tests of early signs of cancer or precancerous lesions. Targeted intervention at this early stage provides the best chance of a cure.

Proteomics is the comprehensive study of proteins associated with a disease. This new technology has enabled researchers to use a combination of biochemistry, biology, and bioinformatics to detect proteins that are expressed in cancer. Proteins are the most likely substance that would produce a successful, useable blood test for pancreatic cancer. We have two experts in the new field of proteomics and full access to costly proteomics equipment.

Using a proteomic approach, we are identifying the proteins that are differentially expressed in pancreatic cancer tissue—this will open a whole new level of knowledge in understanding how pancreatic cancer develops. Such knowledge could lead to new drug development, improved assessment of response after treatment, and potential chemoprevention programs. From our pancreatic cancer proteomic analyses, we hope to develop a blood biomarker that can identify patients who have early pancreatic cancer while it is curable.

Gene Identification

It is likely that hereditary factors play a role in 17% or more of pancreatic cancers. Ten percent of patients have a familial history and another 7% of apparently “sporadic” pancreatic cancer patients carry a genetic mutation that causes the disease. Kindreds, with 2 or more family members who have been diagnosed with pancreatic cancer and who are first degree relatives, are considered to have familial pancreatic cancer (FPC). Not all patients who carry a mutation in a gene that predisposes to pancreatic cancer will get the disease. The lifetime cancer risk for a gene-carrying individual from a FPC kindred can range from 5% to100%, depending upon the gene inherited and environmental-gene interactions. Smoking is the chief environmental risk factor that influences penetrance of pancreatic cancer in these kindreds. Not only does smoking increase the risk of cancer by >3 fold, but it also decreases the age of onset by approximately 10 years.

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